Medical and traumatic emergency conditions affecting the cardiac, respiratory, nervous, and hematologic systems collectively account for the overwhelming preponderance of death and disability affecting Americans. It is imperative that new approaches for timely diagnosis and treatment of these conditions treatments be efficiently developed. This application is to form a Southern California Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SoCal SIREN) Hub and Spoke system that will conduct high-quality, multi-site clinical trials to improve the outcomes for patients with neurologic, cardiac, respiratory, and hematologic, and trauma emergency events. The SoCal SIREN consortium will marshal all six academic medical centers in the region (UCLA, Harbor-UCLA, USC, UCI, UCSD, and Cedars-Sinai); all 3 County EMS agencies [Los Angeles EMS (lead), Orange County EMS (co-lead), and San Diego County EMS (flexible)], and up to 83 potential performance sites (1 Hub, 5 Core Spoke, 16 Additional Spoke, and 61 Flexible Spoke) Medical Centers in Southern California, experienced in performing emergency clinical trials efficiently and excellently. Eleven Advisory Panels with expertise in specific disease and research domains will facilitate trial implementation within the Network and serve as a resource to the Hub leadership and to individual performance sites. The four specific aims of this proposal are to: 1) perform high-quality pragmatic clinical trials in several different types of emergency disorders afflicting adults or children throughout Southern California; 2) facilitate collaboration between emergency medicine physicians and disease specialists throughout Southern California in trial design and execution high quality NSTN recovery and rehabilitaiton trials throughout Los Angeles and Orange Counties; 3) facilitate collaboration between the prehospital EMS system and acute receiving hospitals, including specialty receiving centers in trauma, stroke, and cardiac resuscitation, throughout Southern California in trial design and execution; and 4) ensure participation of a substantial number of patients with emergency conditions in SIREN clinical trials, including women, children, Hispanic-Americans, African-Americans, and other traditionally underrepresented populations.